Where can I find this paper?

http://www.ncbi.nlm.nih.gov/pubmed/26283067

What is this paper about (what is the research question)?

Does S100B, a calcium-binding protein located in the cytoplasm and nucleus of astrocytes and Schwann cells, have a role in predicting intracranial injury (or its absence) for mild head trauma in children?

Summary of the Paper

Design: multicentre prospective cohort study

Objective: to determine the test characteristics for S100B in mild head trauma in children with determination of a cutoff to provide diagnostic utility.

Outcome of interest: diagnostic/predictive performance of S100B biomarker for intracranial injury in children with mild head trauma

Reference Standard: presence of intracranial injury (any collection of blood within the cranial vault or cerebral oedema) on CT scan

Participants: children aged <16 years presenting to one of three Swiss paediatric EDs between January 2009 and December 2011

• Inclusions: patients with mild head injury (acute head trauma with confusion or LOC <30mins or amnesia or transient neurological abnormality) for whom a CT was performed and blood obtained for S100B assay.
• Exclusions: children arriving >6h after head trauma, children with Down syndrome, patients with a history of seizure in the preceding 28/7

Results: 80 children were enrolled of whom 73 were included in the analysis. 20 (27.4%) had evidence of intracranial injury on CT although none required surgical intervention.

The area under the Receiver Operator Characteristic (ROC) curve for S100B was 0.73 (95% CI 0.60-0.86) which improved to 0.77 (95% CI 0.65-0.89) when under 2s were excluded.

Using a cutoff of 0.14micrograms/L gave a sensitivity of 95% (95% CI 77%-100%) for all children [100% (95% CI 81%-100%) with under 2s excluded] and specificity 34.0% (95% CI 27%-36%).

Authors’ Conclusions:

The biomarker S100B is a valuable tool to help the physician decide whether head CT is indicated for children aged <16 years with mild head trauma. Its excellent sensitivity indicates that it could be an accurate tool to “rule out” an intracranial injury.

On the study design

This was a small prospective study in which blood samples were taken from children presenting with mild head injury deemed by clinicians to require CT scan and analysed independently of the CT findings to permit calculation of test characteristics for the biomarker S100B.

The authors included patients under 16 presenting to one of three Swiss paediatric EDs with mild head injury (acute head trauma with confusion or LOC <30mins or amnesia or transient neurological abnormality) for whom a CT was requested; these subjects also had a venous blood sample for S100B level which was not available before CTs had been reported. They then determined test characteristics for S100B in the context of CT findings. The sample size was pretty small – 80 children were enrolled of whom 7 were excluded, either because they didn’t have the blood test at all, within 6h or they didn’t have the CT scan. This affects the applicability of the study.

Performing bloods on children in the ED is a tricky one; children with major trauma presentations frequently have blood tests taken but these children might not. It’s worth considering how many additional blood tests we might be performing if S100B is adopted into everyday practice.

The other interesting thing is the classification of “mild head injury”. These children were selected because they were having CT head (the reference standard for determining the presence or absence of intracranial injury) but the population does not completely correlate with those head injured children who would have a CT indicated according to the NICE head injury guidelines – which is going to affect whether we can directly extrapolate the results to our ED head injured population as there may be some children we would want to CT who would not have been included in this study.

What were the results and what does this mean?

Only 73/80 were included in the analysis, of whom 20 had an intracranial injury. No surgical interventions were required in any case so we may be missing this proportion of severely head injured patients which, combined with the inclusion of only “mild head injuries” means that we have really only looked at a slice of our PED head injury population.

The ROC curve for S100B had an AUC of 0.73 (95% CI 0.60-0.86) which improved to 0.77 (95% CI 0.65-0.89) when under 2s were excluded.

Using a cutoff of 0.14micrograms/L gave a sensitivity of 95% (95% CI 77%-100%) for all children (100% (95% CI 81%-100%) with under 2s excluded) and specificity 34.0% (95% CI 27%-36%). This looks good, but look at the width of those confidence intervals, reflective of the small sample size. If the true sensitivity is 77% that’s no good at all – so we definitely need confirmation with a bigger study and ideally wider inclusion, so we can apply the findings to all our head injured patients.

What can we take from this paper into clinical practice?

There’s definitely potential for S100B to be used as a lesser evil compared with radiation exposure on the developing brain. However the evidence (and, in all likelihood, the assays in your laboratory) isn’t there yet. Watch this space… I suspect there is more to come on S100B.

More questions to ask

• How would S100B perform for all head injured children in a bigger study?
• Do we need to exclude the under-2s to improve test characteristics – and what should we do with those children?
• What is the level of sensitivity we will accept at the cost of specificity?

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